Pancreatic islets of Langerhans are the only organs of insulin production by β cells in the body. However, they have a limited capacity for regeneration. This limited regeneration capacity predisposes mammals to develop diabetes mellitus. Thus there is a need in the art of endocrinology for products which can stimulate the regeneration of islets of Langerhans to prevent or ameliorate the symptoms of diabetes mellitus.
There are many factors regulating pancreatic β cell mass. (Vinik, et al., Diabetes Reviews 4: 235-263, 1996.) A pancreatic extract called ilotropin induces β cell regeneration and reverses diabetes. (Rosenberg et al. (1996) Diabetologia 39: 256-262. A gene encoding a protein within ilotropin has been identified and isolated; the protein is responsible for stimulating islet cell regeneration. (Rafaeloff, R. Journal of Clinical Investigations 99: 2100-2109, 1997.) This protein is called INGAP, and is disclosed in patent applications Ser. Nos. 08/401,530, 08/709,662, and 60/006,271. The disclosure of these applications is expressly incorporated herein. Despite the knowledge of the complete nucleotide sequence of the INGAP gene, expression of the protein has been limited. Thus there is a need in the art for methods of expressing and isolating large quantities of the INGAP protein, especially in eukaryotic systems.